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Clinical Trials

MainTitle

Effects of Ledipasvir/Sofosbuvir on the Pharmacokinetics and Renal Safety of Tenofovir Alafenamide (TAF)

This study is not yet open for participant recruitment. (see Contacts and Locations)

Verified July 2017 by University of Colorado, Denver

Sponsor
University of Colorado, Denver


Information provided by (Responsible Party)
University of Colorado, Denver
ClinicalTrials.gov Identifier
NCT03126370

First received: April 19, 2017
Last updated: July 17, 2017
Last Verified: July 2017
History of Changes
Purpose

Purpose

This study evaluates the effect of ledipasvir/sofosbuvir (LDV/SOF) treatment on the pharmacokinetics (PK) and renal safety of tenofovir in the form of tenofovir alafenamide. Subjects receiving tenofovir-based antiretroviral therapy with human immunodeficiency virus (HIV), and also taking a ritonavir or cobicistat boosted protease inhibitor who are initiating LDV/SOF treatment for Hepatitis C virus (HCV) will be invited to participate. The study consists of seven visits: a screening visit and three abbreviated 4-hour pharmacokinetic visits, and three standard of care visits (week 8 and 12 of LDV/SOF treatment and one visit to assess cure).

Condition Intervention Phase
Hepatitis C
HIV Coinfection

Drug : LDV/SOF and TAF
Phase 4

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Effects of Ledipasvir/Sofosbuvir Treatment on the Pharmacokinetics and Renal Safety of Tenofovir Alafenamide (TAF) in Patients With HIV.

Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures

  • Change in area under the plasma concentration (AUC) of tenofovir [ Time Frame: Over the course of 28 weeks, will be assessed at 12 weeks, 24 weeks and 28 weeks. ]
    Compare tenofovir AUC0-24 before and after switching from TDF to TAF, and before and after administration of LDV/SOF
  • Change in tenofovir diphosphate in peripheral blood mononuclear cells [ Time Frame: Over the course of 28 weeks, will be assessed at 12 weeks, 24 weeks and 28 weeks. ]
    Compare tenofovir diphosphate (TFV-DP) in peripheral blood mononuclear cells (PBMC's) when tenofovir is given as TDF and then switched to TAF and also when TAF is given with LDV/SOF
Secondary Outcome Measures:
  • Change in tenofovir diphosphate in dried blood spots [ Time Frame: 24 weeks ]
    Compare tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) when tenofovir is given as TDF and then switched to TAF and also when TAF is given with LDV/SOF
  • Change in Estimated Glomerular Filtration Rate (eGFR) [ Time Frame: Over the course of 28 weeks, will be assessed at 12 weeks, 24 weeks and 28 weeks. ]
    Compare eGFR calculated using Modification of Diet in Renal Disease (MDRD) equation before and after the addition of LDV/SOF

Estimated Enrollment: 15
Study Start Date: August 2017
Estimated Study Completion Date: December 31, 2018
Estimated Primary Completion Date: December 31, 2018 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: LDV/SOF and TAF
Subjects who are already taking tenofovir disoproxil fumarate 300mg/emtricitabine 200mg (Truvada) in combination with either a ritonavir or cobicistat boosted protease inhibitor, and who have both HIV and HCV will be switched to tenofovir alafenamide 25mg/emtricitabine 200mg (Descovy). After taking tenofovir alafenamide/emtricitabine for 12 weeks subjects will then start taking ledipasvir 90mg/sofosbuvir 400mg (Harvoni) for treatment of their HCV for 12 weeks in combination with the tenofovir alafenamide 25mg/emtrcitabine 200mg (Descovy)
Drug: LDV/SOF and TAF
  • Subjects will be switched from tenofovir disoproxil fumarate to tenofovir alafenamide and then once on tenofovir alafenamide for 12 weeks, subjects will be given concominant ledipasvir/sofosbuvir for 12 weeks
  • Other: Blood draws for tenofovir PK, renal function assessment

Eligibility

Eligibility

Ages Eligible for Study: 18 Years to 70 Years  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  

Criteria

Inclusion Criteria:

  • Have been taking tenofovir and a ritonavir- or cobicistat-boosted PI for at least 30 days as part of standard care
  • HCV RNA <48 copies/mL at most recent clinic visit


Exclusion Criteria:
  • eGFR < 30 mL/min
  • Pregnant or planning pregnancy
  • Breastfeeding
  • Any medical, social, or mental-health issue(s) that, in the opinion of the investigators, could interfere with study participation or the study outcomes
  • Signs or symptoms of decompensated liver disease
  • HCV treatment-experienced with cirrhosis

contacts and locations

Contacts and Locations

Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03126370

Contacts

Contact:   Jennifer J Kiser, PharmD 303-724-6131 jennifer.kiser@ucdenver.edu
Contact:   Christine E MacBrayne, PharmD 303-724-9580 christine.macbrayne@ucdenver.edu

Locations

United States, Colorado
University of Colorado Hospital Not yet recruiting
Aurora, Colorado, United States, 80045
Contact: Jennifer J Kiser, PharmD    303-724-6131    jennifer.kiser@ucdenver.edu
Contact: Christiine E MacBrayne, PharmD    303-724-9580    christine.macbrayne@ucdenver.edu

Sponsors and Collaborators

University of Colorado, Denver

Investigators

Principal Investigator: Jennifer J Kiser, PharmD University of Colorado, Denver
More Information

More Information


Responsible Party: University of Colorado, Denver  
ClinicalTrials.gov Identifier: NCT03126370   History of Changes  
Other Study ID Numbers: 17-0490  
Study First Received: April 19, 2017  
Last Updated: July 17, 2017  

Studies a U.S. FDA-regulated Drug Product: Yes  
Studies a U.S. FDA-regulated Device Product: No  
Product Manufactured in and Exported from the U.S.: No  

Additional relevant MeSH terms:
Hepatitis C
Coinfection
Tenofovir
Sofosbuvir
Ledipasvir
Ledipasvir, sofosbuvir drug combination

ClinicalTrials.gov processed this data on October 18, 2017
This information is provided by ClinicalTrials.gov.